title: Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma.
abstract: OBJECTIVE
  Montelukast, a cysteinyl leukotriene receptor 1 antagonist, is safe and efficacious in patients with asthma. The mechanisms underlying the significant interpatient variability in response to montelukast are not clear but are believed to be, in part, because of genetic variability.
  
  
  METHODS
  To examine the associations between polymorphisms in candidate genes in the leukotriene pathway and outcomes in patients with asthma on montelukast for 4-8 weeks, we evaluated the changes in peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1·0) ) and patients' subjective symptom before and after montelukast treatment. DNA was collected from 252 Japanese participants.
  
  
  CONCLUSIONS
  Two single-nucleotide polymorphisms (SNPs) in the ALOX5 (rs2115819) and LTA4H (rs2660845) genes were successfully typed. There was no difference between members of the general population (n = 200) and patients (n = 52) in each genotype frequency. Significant associations were found between SNP genotypes in the LTA4H gene and changes in PEF and FEV(1·0) . The PEF and FEV(1·0) responses to montelukast in the A/A genotypes (n = 4) for the LTA4H SNP were significantly higher than those in the G allele carriers (A/G+G/G) (n = 17).
  
  
  CONCLUSIONS
  Despite the small sample size, our results suggest that genetic variation in leukotriene pathway candidate genes contributes to variability in clinical responses to montelukast in Japanese patients with asthma.
authors.affiliation: Division of Clinical Sciences and Neuropsychopharmacology, Meijo University Graduate School of Pharmaceutical Sciences, Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kotani
authors.forename: R
authors.initials: R
authors.lastname: Kishi
authors.forename: A
authors.initials: A
authors.lastname: Mouri
authors.forename: T
authors.initials: T
authors.lastname: Sashio
authors.forename: J
authors.initials: J
authors.lastname: Shindo
authors.forename: A
authors.initials: A
authors.lastname: Shiraki
authors.forename: T
authors.initials: T
authors.lastname: Hiramatsu
authors.forename: S
authors.initials: S
authors.lastname: Iwata
authors.forename: H
authors.initials: H
authors.lastname: Taniguchi
authors.forename: O
authors.initials: O
authors.lastname: Nishiyama
authors.forename: M
authors.initials: M
authors.lastname: Iwata
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Gonda
authors.forename: T
authors.initials: T
authors.lastname: Niwa
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Kume
authors.forename: Y
authors.initials: Y
authors.lastname: Noda
mesh_terms: D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000483:Alleles; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics; D003521:Cyclopropanes; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005838:Genotype; D006801:Humans; D007564:Japan; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D015289:Leukotrienes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D020641:Polymorphism, Single Nucleotide; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D013440:Sulfides; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011804:Quinolines; D013440:Sulfides; D001094:Arachidonate 5-Lipoxygenase; D004851:Epoxide Hydrolases; C093875:montelukast; C043134:leukotriene A4 hydrolase